Structure analysis of thymidylate synthase from white spot syndrome virus reveals WSSV-specific structural elements.

International Journal of Biological Macromolecules
Vipul PanchalDileep Vasudevan

Abstract

White spot syndrome virus (WSSV), the causative agent of white spot disease (WSD) severely affecting crustacean life forms, is highly contagious and forms the principal cause of massive economic losses in the shrimp aquaculture industry. Previous studies have demonstrated thymidylate synthase as a successful anti-cancer therapeutic drug target, leading to various anti-cancer drugs. The differential utilization of nucleotide precursors between white spot syndrome virus and shrimp encouraged us to analyze WSSV-thymidylate synthase (wTS). Here, we report the crystal structures of wTS in its apo-form and as a ternary complex with deoxyuridine monophosphate (dUMP) and methotrexate at a resolution of 2.35 Å and 2.6 Å, respectively. wTS possesses a fold characteristic to known thymidylate synthase (TS) structures. Like other TS structures, the apo-form of wTS displays an open conformation, whereas the wTS ternary complex attains a closed conformation. While the C-terminal loop maintains a typical distance from methotrexate, the Sγ atom of the catalytic Cys is positioned farther from the C6 atom of dUMP. Altogether, we report the first TS structure from a crustacean virus and highlight its distinction from shrimp and other TS structures.

References

Jul 1, 1997·Protein Expression and Purification·J Pedersen-LaneF Maley
Aug 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·D A ErlansonJ A Wells
Jun 27, 2002·Biochimica Et Biophysica Acta·M Paola CostiRobert M Stroud
Jun 26, 2004·The Journal of General Virology·Qin LiFeng Yang
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jun 6, 2006·Journal of Biochemistry·Changqing DuXiukun Lin
Feb 26, 2010·Veterinary Research·Arturo Sánchez-Paz
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·T Geoff G BattyeAndrew G W Leslie
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Mar 22, 2012·Journal of Invertebrate Pathology·D V LightnerS A Navarro
Mar 22, 2012·Journal of Invertebrate Pathology·G D StentifordD V Lightner
Apr 17, 2012·Acta Crystallographica. Section D, Biological Crystallography·Pavel V AfoninePaul D Adams
Sep 6, 2012·Acta Crystallographica. Section D, Biological Crystallography·Cecilia PozziStefano Mangani
Nov 17, 2012·Open Biology·Tamara BastaHannu Myllykallio
Apr 25, 2013·Journal of the American Chemical Society·Zhen WangAmnon Kohen
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans, Garib N Murshudov
Sep 10, 2013·Current Opinion in Immunology·G Lynn LawMichael G Katze
May 20, 2017·Acta Virologica·G M TandelM J Prince Jeyaseelan
Oct 27, 2017·Protein Science : a Publication of the Protein Society·Christopher J WilliamsDavid C Richardson
May 16, 2018·Trends in Microbiology·Beatrice MercorelliArianna Loregian
Mar 6, 2019·Nature Microbiology·Maya A Farha, Eric D Brown

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